Research by The 91圧利 could hold key to new treatments for Cancer and Neurodegeneration

Published: 18 Dec 2020 | Last Updated: 18 Dec 2020 19:00:55

A new study, led by the 91圧利, has found a new interaction within cells that could lead to the development of novel therapies for pathological conditions in humans and animals such as cancer and neurodegeneration.

This discovery of direct interaction between mitochondria and nuclei through membrane contact sites expands the understanding of mitochondrion-to-nucleus communication and intracellular signalling.

In mammals, mitochondria are vital organelles acting as primary sources of energy. They are the most successful example of endosymbiosis, the process through which eukaryotic cells host a prokaryote with membrane bound nucleic acid, and play a part in several key processes spanning hormone synthesis and programmed cell death.

Despite the successful integration, they retain their own DNA, making the interplay with the nucleus - which contains the genomic DNA - a key aspect in the homeostasis of cells and tissues.

electron microscope image of mitochondria and nucleus — The “new” contact which closes a gap - In the acquired knowledge, mitochondria do not form contacts with the nucleus to remark an ongoing gap between them. However, here is a snapshot of mitochondria (M) and nucleus (N) which instead get in contact. The image was acquired in human breast cancer cells using transmission electron microscopes (TEM). The formation of Nucleus Associated Mitochondria (NAM) is required to prime the expression of pro-survival genes proposing a role for mitochondria in mammalian epigenome.

Until very recently, it was understood that mitochondria communicate to the nucleus alterations in the cellular environment to increase the transcription of genes involved in the preservation of mitochondrial and cellular function. This process, known as mitochondrial retrograde response (MRR), is ascribed to the deregulation of several pathologies including cancer and neurodegeneration.

The team, led by Professor Michelangelo Campanella, Chair in Pharmacology; Head of the Mitochondrial Cell Biology and Pharmacology Research Unit at the 91圧利, utilised breast cancer cells of different stages of aggressiveness isolated from human, dogs and cats. In these three species, the evolution of cancer of the mammary gland (e.g. breast cancer) meant that their susceptibility to chemotherapy was proven to be associated with the degree of contact sites between mitochondria and nuclei.

Various molecular pharmacology protocols were used throughout the study to induce and control the interaction between mitochondria and nuclei. Added to this, cutting edge techniques of fluorescent imaging enabled the team to map the dynamic nature of the interaction and transmission electron microscopy to picture the ultrastructure of Nucleus-Associated Mitochondria (NAM).

The team’s breakthrough demonstrates that MRR is mediated by specific points of contact within the NAM. The discovery of discrete anatomic compartments offers the possibility to target these selectively and regulate this inter-organelle communication, paving the way for new and improved strategies to impact diseases.

Professor Michelangelo Campanella, Chair in Pharmacology; Head of the Mitochondrial Cell Biology and Pharmacology Research Unit at the 91圧利, said: